Jennifer L. Gibbs, D.D.S., Ph.D. was appointed as an Assistant Adjunct Professor after completing her Endodontic Residency in July 2008. She has prior training in systems neuroscience research including biochemical assays, cell culture, anatomical studies, and behavioral experiments. This K-23 Mentored Patient-Oriented Research Career Development Award will be used to launch her career in translational orofacial pain research with a focus on understanding the mechanisms of neuropathic pain (NP). Research Plan: Dr. Gibbs has propsed a series of studies to evaluate the role of capsaicin-sensitive primary afferent neurons in mediating NP by performing a cross-sectional study on subjects diagnosed with post- herpetic neuralgia (PHN) and a complementary series of studies in animals using a model of orofacial NP. In these studies we will determine the relationship between a capsaicin response test (CRT) and outcomes of pain and sensory measures consistent with hyper-responsive primary afferents to determine if the CRT faciliatates a mechanism-based diagnosis of NP. In addition we will test the hjqjothesis that PHN subjects who respond to capsaicin have distinct epidermal and dermal innervation patterns and determine whether histological evaluation of skin biopsies can identify a biomarker for mechanism-based classification of NP. Finally, an animal model will be used to study the contribution of peripheral versus central terminals of capsaicin sensitive primary afferents in the setting of nerve injury Development Plan:Dr. Gibbs will continue her previously initiated work with Dr. Allan Basbaum in his laboratory studying basic mechanisms of pain and relevant techniques including neuroanatomy and pain behavior. In addition Dr. Gibbs will work with Dr. Rowbotham at the UCSF Pain Clinical Research Center to conduct sensory testing studies and collect biopsies from PHN subjects. Dr. Gibbs will continue collaborative efforts with Dr. Schmidt to identify biomarkers for NP and develop a new model of orofacial pain in animals. Dr. Gibbs is also currently pursuing a Master's in Clinical Reseach to facilitate her ability to perform translational research. Dr. Gibbs has the full support ofher home department and will transition to a tenure track position in July 2009. RELEVANCE (See instructions): These studies will yield novel and important insights into the mechanisms contributing th NP and help define populations (e.g. capsaicin responders) who are more likely to benefit from mechanims targeting analgesic therapies. Neuropathic pain has devastating impact on patients ability to inderact socially, work, and overall enjoyment of life. Improvement in diagnosis of NP is critical for better management of these patients.